This study is being submitted for review under the R21 (exploratory grant) mechanism, Its purpose is to explore whether the addition of very low doses of naltrexone to a methadone tapering schedule for opiate detoxification is safe, decreases withdrawal intensity and enhances patient treatment compliance. Although many different techniques for opiate detoxification have been employed, there is a continuing search for more effective approaches to reduce the duration and discomfort of withdrawal. Recent attempts have included the use of opiate antagonists to induce "ultra rapid" detoxification. However, the resulting need for heavy sedation or anesthesia to control withdrawal intensity and the increased possibility of medical complications has discouraged and limited the use of this approach. By contrast, there is experimental evidence that very low doses of naltrexone administered in the presence of opiates has analgesic and dependency reducing properties, suggesting that the use of very low dose naltrexone in the clinical management of opiate detoxification might be a useful strategy. To test this hypothesis, 360 volunteer opiate dependent subjects, admitted to the inpatient detoxification program of a community hospital and placed on a 4-day detoxification schedule, will be randomly assigned to receive one of three different low-dose naltrexone schedules or placebo in addition to their routine methadone tapering treatment. The four groups will be compared with respect to behavioral, biological and subjective withdrawal signs and symptoms, detoxification completion rates, acceptance of referral to outpatient treatment, and one and seven day post-detoxification follow-up evaluations. If the administration of low-dose naltrexone (antagonist) at the same time as methadone (agonist) is found to be more effective than placebo in reducing withdrawal discomfort, the findings will have clear treatment implications and raise important questions about the mechanisms of opiate agonist and antagonist interactions at the receptor.